AG-041R is a cholecystokinin-B/gastrin receptor (Gastrin/CCK-B) antagonist [1]. The Gastrin/CCK-B receptor is a regulator of gastric acid secretion and mucosal growth. The Gastrin/CCK-B is abundantly expressed in mammalian stomach [2].

In vitro: In rabbit primary chondrocytes, AG-041R (0.1 μM) stimulated the cell growth and proliferation, but suppressed with 10 μM. Treatment with AG-041R (1 μM) for 28 days accelerated the chondrocyte growth and increased the cell number [1]. In chondrocytes incubated with 0.1 and 1 μM AG-041R, synthesis of GAG increased with culture, and amounts accumulated in the composites increased [1]. 10 μM AG-041R might be even toxic to the cells and total RNA levels [1]. The ratio of the amounts of two chondroitin sulfate isomers, chondroitin-6-sulfate to chondroitin-4-sulfate, an indicator of cartilage maturation, increased with 1 μM but decreased with 10 μM AG-041R [1].

In vivo: In a preclinical toxicological study on rats, oral administration of high dose of AG-041R stimulated systemic cartilage hyperplasia, including the trachea, the intervertebral disk and the articular cartilage. Daily intraarticular injection of AG-041R for 3 weeks into rat knee joints also induced cartilage hyperplasia in marginal regions of the femoral condyle without affecting other tissues [1].

References:[1] Ochi M, Kawasaki K, Kataoka H, et al. AG-041R, a gastrin/CCK-B antagonist, stimulates chondrocyte proliferation and metabolism in vitro[J]. Biochemical and biophysical research communications, 2001, 283(5): 1118-1123.[2] Langhans N, Rindi G, Chiu M, et al. Abnormal gastric histology and decreased acid production in cholecystokinin-B/gastrin receptor-deficient mice[J]. Gastroenterology, 1997, 112(1): 280-286.